The purpose of this study is to evaluate whether PET/CT-RGD or MIBI can be used for the angiogenesis assessment of NL003 in PAD patients.
Hepatocyte growth factor (HGF) gene therapy has been shown to be a potential choice for CLI patients without surgical option. NL003, which is a DNA plasmid that contains novel genomic cDNA hybrid human HGF coding sequence (HGF-X7) expressing two isoforms of HGF, HGF 728 and HGF 723. Animal studies showed that NL003 inducing angiogenesis in the affected limb and result in an increase in tissue perfusion. Our previous phase II clinical trial has suggested the successful limb-salvaging capacity of NL003 in treatment of patients with CLTI. In this study we will use 68Ga RGD PET/CT and 99mTc MIBI SPECT imaging methods to evaluate the effect of NL003 on angiogenesis and lower limb blood flow perfusion during the treatment of chronic lower limb ischemia, and evaluated the effectiveness and safety of the drug. The subjects will be randomly divided into the investigational drug group and the placebo group in a 1:1 ratio. NL003 or placebo will be injected into the muscle of the affected limb on D0, D14 and D28, 0.5mg/0.5mL/site, total 8mg, 32 sites. PET/CT will be measured on D14, D42 before drug administration, MIBI SPECT imaging will be collected on D60.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
Day 0: 8mg of NL003 (32 injections of 0.5ml of NL003) Day 14: 8mg of NL003 (32 injections of 0.5ml of NL003) Day 28: 8mg of NL003 (32 injections of 0.5ml of NL003)
Day 0: 16ml of Normal Saline (32 injections ) Day 14: 16ml of Normal Saline (32 injections ) Day 28: 16ml of Normal Saline (32 injections ) Other Name: Placebo
Peking Union Medical College Hospital
Beijing, Beijing Municipality, China
RECRUITINGChanges of the new blood vessels number
changes in the number of new blood vessels measured by PETCT-RGD on D14 and D42, compare with that of the baseline.
Time frame: Day 14、Day 42
Changes of local blood perfusion
the changes of local blood perfusion measured by MIBI on D60, compare with that of baseline.
Time frame: Day 60
Changes to the ABI from the baseline
Ankle-brachial index (ABI) refers to the ratio of systolic blood pressure of the anterior tibial artery (dorsal foot artery) or posterior tibial artery to the systolic blood pressure of the brachial artery.Participants were tested for ankle-brachial index (ABI).
Time frame: Day 60
Laser Speckle Imaging changes in blood flow from the baseline
Laser Speckle Imaging changes in blood flow from the baseline was measured on D60.
Time frame: Day 60
Changes of pain score from the baseline
The severity of critical Limb ischemia was assessed by Rutherford grading at screening、D14、D28、D42、D60、D90
Time frame: Day 14、Day 28、Day 42、Day 60、Day 90
Gangrene /Ulcer changes from the baseline
Changes in the area of ulcer or gangrene from baseline after use of the study drug
Time frame: Day 14、Day 28、Day 42、Day 60、Day 90
Changes in quality of life scores from baseline
The quality of life score questionnaire was conducted to evaluate the subjective perception of Critical Limb Ischemia, including the subjects' perception of quality of life, health, or other aspects of life.
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Time frame: Day 60